A paraventricular hypothalamic nucleus input to ventral of lateral septal nucleus controls chronic visceral pain

Irritable bowel syndrome is a functional gastrointestinal disorder characterized by chronic visceral pain with complex etiology and difficult treatment. Accumulated evidence has confirmed that the sensitization of the central nervous system plays an important role in the development of visceral pain, whereas the exact mechanisms of action of the neural pathways remain largely unknown. In this study, a distinct neural circuit was identified from the paraventricular hypothalamic (PVH) to the ventral of lateral septal (LSV) region. This circuit was responsible for regulating visceral pain. In particular, the data indicated that the PVH CaMKII alpha-positive neurons inputs to the LSV CaMKII alpha-positive neurons were only activated by colorectal distention rather than somatic stimulations. The PVH-LSV CaMKII alpha(+) projection pathway was further confirmed by experiments containing a viral tracer. Optogenetic inhibition of PVH CaMKII alpha(+) inputs to LSV CaMKII alpha-positive neurons suppressed visceral pain, whereas selective activation of the PVH-LSV CaMKII alpha(+) projection evoked visceral pain. These findings suggest the critical role of the PVH-LSV CaMKII alpha(+) circuit in regulating visceral pain.